Flavivirus comprise more than 70 different viruses, many of which are arthropod-borne and transmitted by either mosquitoes or ticks.
Flavivirus is a genus of viruses in the family Flaviviridae. This genus includes the West Nile virus (WNV), dengue virus (DENV), tick-borne encephalitis virus (TBEV), yellow fever virus (YFV), Japanese encephalitis (JEV), hepatitis C virus (HCV) and several other viruses which may cause encephalitis or haemorrhagic diseases.
Dengue fever is a mosquito-borne disease caused by the flavivirus and has spread to most tropical and many subtropical areas. The disease is caused by four closely related viruses, the Dengue virus 1 including subtypes I to IV, Dengue virus 2 including subtypes Asian I, Asian II, Cosmopolitan, American and American/Asian, Dengue virus 3 including subtypes I to IV and Dengue virus 4 including subtypes I to III. Although Dengue is the most important flavivirus with respect to global disease incidence, the development and use of vaccines against the virus has been hampered so far by the theoretical risk of vaccine-related adverse events such as immune enhancement of infection and the requirement to induce a long-lasting protective immune response against all four dengue serotypes simultaneously.
There is no effective dengue therapeutic and prevention against dengue fever is currently limited to vector control measures. A dengue vaccine would therefore represent a major advance in the control of the disease.
While no licensed dengue vaccine is available, several vaccine candidates are currently evaluated in clinical studies. WHO indicates that the growing global epidemic of dengue is of mounting concern, and a safe and effective vaccine is urgently needed. www.who.int/immunization/research/development/dengue_vaccines/en/) and Vaccine 30 (2012) 4301-4306).
Virus-like particles (VLPs) are multiprotein structures that mimic the organization and conformation of authentic native viruses but non-infectious because they do not contain any viral genome, potentially yielding safer vaccine candidates. A handful of prophylactic VLP-based vaccines is currently commercialized worldwide: GlaxoSmithKline's Engerix® (hepatitis B virus) and Cervarix® (human papillomavirus), and Merck and Co., Inc.'s Recombivax HB® (hepatitis B virus) and Gardasil® (human papillomavirus) are some examples. Other VLP-based vaccine candidates are in clinical trials or undergoing preclinical evaluation, such as, influenza virus, parvovirus, Norwalk and various chimeric VLPs. Many others are still restricted to small-scale fundamental research, despite their success in preclinical tests. The implications of large-scale VLP production are discussed in the context of process control, monitorization and optimization. The main up- and down-stream technical challenges are identified and discussed accordingly. Successful VLP-based vaccine blockbusters are briefly presented concomitantly with the latest results from clinical trials and the recent developments in chimeric VLP-based technology for either therapeutic or prophylactic vaccination.
Up to now, VLP-based vaccines have been produced for more than 30 different viruses that infect human and other animals. The examples include AAV (Adeno-associated virus), H5N3 (Avian influenza), BFDV (Budgerigar fledgling disease virus), BTV (Bluetongue virus), Ebola, Enterovirus 71, GHPV (Goose hemorrhagic polyoma virus), HBV (Hepatitis B virus), HCV (Hepatitis C virus), HDV (Hepatitis δ virus), HEV (Hepatitis E virus), HIV, HPV (Human papillomavirus), IBDV (Infectious bursal disease virus), Influenza A, Influenza A H1N1, Influenza A H3N2, JC polymavirus, Margurg, MS2, IPCV (Indian peanut clump virus), NDV (Newcastle disease virus), No (Norovirus) Nv (Norwalk virus), PhMV (Physalis mottle virus), Polymavirus, PPV (Porcine parvovirus), RHDV (Rabbit hemorrhagic disease virus), Rotavirus, SARS, SIV (Simian immunodeficiency virus), SV40 (Simian virus 40), SVDV (Swine vesicular disease virus) and so on. (Expert Rev. Vaccines 9(10), 1149-1176, 2010).